- HETEROCYCLIC COMPOUND
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Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.
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Page/Page column 62
(2013/02/28)
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- OXOBENZINDOLIZINOQUINOLINES AND USES THEREOF
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The synthesis of aromathecins, substituted 12H-5,l la-diazadibenzo[b,h]fluoren- 11 -ones is described. Use of these cytotoxic compounds and pharmaceutical compositions containing them for the treatment of cancer is described. Two novel processes for the synthesis of this system and a series of 14-substituted aromathecins as novel cytotoxic, topoisomerase I poisons are described.
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Page/Page column 30
(2009/12/23)
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- Design, synthesis, and biological evaluation of 14-substituted aromathecins as topoisomerase I inhibitors
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The aromathecin or "rosettacin" class of topoisomerase I (top1) inhibitors is effectively a "composite" of the natural products camptothecin and luotonin A and the synthetic indenoisoquinolines. The aromathecins have aroused considerable interest following the isolation and total synthesis of 22-hydroxyacuminatine, a rare cytotoxic natural product containing the 12H-5,11a-diazadibenzo[b,h]fluoren-11-one system. We have developed two novel syntheses of this system and prepared a series of 14-substituted aromathecins as novel antiproliferative topoisomerase I poisons. These inhibitors are proposed to act via an intercalation and "poisoning" mechanism identical to camptothecin and the indenoisoquinolines. Many of these compounds possess greater antiproliferative activity and anti-top 1 activity than the parent unsubstituted compound (rosettacin) and previously synthesized aromathecins, as well as greater top1 inhibitory activity than 22-hydroxyacuminatine. In addition to potentially aiding solubility and localization to the DNA-enzyme complex, nitrogenous substituents located at the 14-position of the aromathecin system have been proposed to project into the major groove of the top1-DNA complex and hydrogen-bond to major-groove amino acids, thereby stabilizing the ternary complex.
- Cinelli, Maris A.,Morrell, Andrew,Dexheimer, Thomas S.,Scher, Evan S.,Pommier, Yves,Cushman, Mark
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experimental part
p. 4609 - 4619
(2009/07/04)
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- Synthesis and biological studies of novel 2-aminoalkylethers as potential antiarrhythmic agents for the conversion of atrial fibrillation
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A series of 2-aminoalkylethers prepared as potential antiarrhythmic agents is described. The present compounds are mixed sodium and potassium ion channel blockers and exhibit antiarrhythmic activity in a rat model of ischemia-induced arrhythmias. Structure-activity studies led to the identification of three compounds 5, 18, and 26, which were selected based on their particular in vivo electrophysiological properties, for studies in two canine atrial fibrillation (AF) models. The three compounds converted AF in both models, but only compound 26 was shown to be orally bioavailable. Resolution of the racemate 26 into its corresponding enantiomers 40 and 41 and subsequent biological testing of these enantiomers led to the selection of (1S,2S)-1-(1-naphthalenethoxy)-2-(3- ketopyrrolidinyl)cyclohexane monohydrochloride (41) as a potential atrial selective antiarrhythmic candidate for further development.
- Plouvier, Bertrand,Beatch, Gregory N.,Jung, Grace L.,Zolotoy, Alexander,Sheng, Tao,Clohs, Lilian,Barrett, Terrance D.,Fedida, David,Wang, Wei Q.,Zhu, Jeff J.,Liu, Yuzhong,Abraham, Shlomo,Lynn, Leah,Dong, Ying,Wall, Richard A.,Walker, Michael J. A.
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p. 2818 - 2841
(2008/02/09)
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- AMINOCYCLOHEXYL ETHER COMPOUNDS AND USES THEREOF
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Aminocyclohexyl ether compounds of formula (I), or a solvate or pharmaceutically acceptable salt thereof: are disclosed. In said formula, A, X and R, -R5 have the meanings given in the description. The compounds of the present invention may be inco
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- Preparation and in Vitro and in Vivo Evaluation of Quinolones with Selective Activity against Gram-Positive Organisms
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A series of quinolones were prepared which contained oximes or substituted oximes as replacements for the amine substituents normally found on the pyrrolidine or piperidine fragments of quinolone antibacterial agents.These substituents led to compounds that had selective activity against Gram-positive organisms.These compounds showed in vivo activity Staphylococcus aureus.Only compound 29 had in vivo activity against Streptococcus pneumoniae.
- Cooper, Curt S.,Klock, Pamela L.,Chu, Daniel T. W.,Hardy, Dwight J.,Swanson, Robert N.,Plattner, Jacob J.
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p. 1393 - 1398
(2007/10/02)
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